Background: Newborns are at high risk of developing respiratorydistress in the immediate post-natal period. Traditionally, they weremanaged by intubation and mechanical ventilation. In recent years, use ofcontinuous positive airway pressure (CPAP) has gained immense popularityas the primary mode of respiratory support in these infants. Its use has beenassociated with reduced need for mechanical ventilation and associated lunginjury.Objectives: To evaluate the immediate outcome of these neonates,to study the predictors associated with failure of CPAP and to devise aclinical score for predicting its failure.Patient and Methods: We prospectively observed 80 neonatesinitiated on nasal CPAP for respiratory distress in the first 24 h of life.CPAP was administered using short binasal prongs and nasal mask CPAP.Results: Primary outcomes of the study were success group thatincluded 48 neonates (60%). While CPAP failure group, who requiredmechanical ventilation after CPAP failure, included 32 neonates (40%). Therelative risk ratio was > 1 for maternal hypertension, premature rupture ofmembranes and Downes score parameters (RRR: 3.36, 6.81and 11respectively) for developing CPAP failure. Stepwise logistic multiregressionanalysis showed that both the gestational age and maximal-FiO2were the best sensitive independent parameters that can predict CPAPfailure. It was found that the best cutoff GA is 31 weeks and the maximal -FiO2 is 50 %. The clinical scoring system thus developed had 100%sensitivity and 96.9% specificity for prediction of CPAP failure (area undercurve: 0.958).Conclusion: A simple clinical score was devised comprising twovariables namely, gestational age at 31 weeks and maximal -FiO2 at 50 %that would predict failure of nasal CPAP in infants with respiratory distresswith relatively high accuracy. This represents the predictive score, abovewhich the CPAP therapy will fail while below it the CPAP therapy willsucceed.